PROJECT SUMMARY Alcohol dependence (AD) is a US public health and safety concern, urging improved treatment approaches such as targeted pharmacotherapies. Preclinical and postmortem data have provided evidence that endocannabinoid signaling may play a role in the initiation and maintenance of alcohol abuse. In this regard, converging data suggest that the metabolizing enzyme, Fatty Acide Amide Hydrolase (FAAH) is deficient in AD; however no in vivo clinical data exist. Our center has recently developed a positron emission tomography (PET) imaging probe, [11C]CURB, which enables measuring FAAH activity in vivo. We have recently shown that brain [11C]CURB binding can be reliably measured in the human, making it possible, for the first time, to measure endocannabinoid metabolism directly in humans with addictive disorders. Here, we will test the hypothesis that FAAH activity is decreased in alcohol dependent patients in early and protracted abstinence relative to control subjects without alcohol use disorder. Fifteen subjects with AD will be scanned with [11C]CURB within 3-7 days of admission from on-going drinking and after 2-4 weeks of supervised abstinence. Healthy controls will be scanned once. Behavioral and demographic information will be recorded and an MRI will be acquired for PET image co-registration. If FAAH activity is shown to be reduced in AD, this would demonstrate an endocannabinoid elevating process that may contribute to both, risk for AD and key features of alcohol use. This could lead to developing therapeutic strategies for prevention and treatment of AD.